The kidney contains several distinct epithelia that, in their aggregate function, are responsible for formation of the urine and the maintenance of fluid and electrolyte homeostasis. Each epithelium has a unique population of sodium and chloride ion transporters and urea transporters, as well as water channels (aquaporins, which in aggregate regulate NaCl and water excretion. Understanding the regulation of these transporters is a key to the ultimate understanding of the pathophysiology of essential hypertension, salt retention in congestive heart failure and disorders of water balance. We are investigating these epithelia and their transporters using a combination of methodologies based on proteomics and oligonucleotide array technologies and the development of transgenic mice, as well as classical immunochemical and transport measurements in isolated perfused tubules. The current focus is on: 1) mechanisms of NaCl retention in hypertension and in extracellular fluid volume expanded states (congestive heart failure, cirrhosis, nephrotic syndrome); 2) the molecular physiology of the urinary concentrating mechanism with emphasis on the role of urea transporters and aquaporins; 3)development and characterization of polyclonal antibodies against renal transporter and channel proteins; 4) molecular physiology of renal NaCl transport regulation including regulation of the epithelial sodium channel (ENaC) by vasopressin and aldosterone; 5) mathematical modeling of renal transport and signaling processes.